The product of the retinoblastoma susceptibility gene (RB1), a 110 kD nuclear protein, has been implicated in the etiology of a variety of human tumors. In addition to rare retinoblastomas, alteration of RB1 function is likely a major contributing factor in the development of cervical carcinomas. In the majority of cervical carcinomas, the inactivation of the function of the Rb protein is a consequence of the ability of a product of the human papillomavirus gene E7 product to form a complex with Rb.
Until now, the normal function of the Rb protein has been unknown. It has been clear that vital oncoproteins such as adenovirus E1A, SV40 T antigen, and human papillomavirus E7 can target the Rb protein, forming a physical complex that has been believed inactive with respect to Rb function. See Dyson et al., Science 243, 934-937 (1989); Whyte et al., Nature 334, 124-129 (1988); DeCaprio et al., Cell 54, 275-283 (1988). It is also believed that this action of E7 is likely an important event in the development of a majority of human cervical carcinomas. Scheffner et al., Proc. Natl. Acad. Sci. USA 88, 5523-5527 (1991). Therefore, therapeutic strategies to intervene in this process would be directed at disrupting this interaction, resulting in a release of Rb so as to allow it to return to its normal function. Until now, this normal function has been unknown. The present invention is based upon our ongoing research in this area.